Plasmodium-infected red blood cells exhibit enhanced rolling independent of host cells and alter flow of uninfected red cells

Abstract

The pathogenicity of Plasmodium falciparum results from its unique ability to adhere to endothelium and uninfected erythrocytes. It is, therefore, important to understand the events leading to flowing blood cells undergoing such adhesion. Largely based on the leukocyte adhesion model, it is postulated that the slowing down (rolling) of Plasmodium-infected red blood cells (PRBCs) is initiated by interactions between certain host adhesion molecules and the parasite proteins. In this article we present data demonstrating that PRBCs do not require the presence of host adhesion molecules to slow down and roll. In a synchronized culture, the proportion of slow-flowing cells increased with parasite development and was highest at the trophozoite stage. We also observed that the uninfected red cells (URBCs), originating from a parasite culture containing PRBCs, were also inherently slower compared to malaria-unexposed normal red blood cells (NRBCs). NRBCs became slower upon incubation with supernatant taken from a parasite culture. However, such an effect was transient and the NRBCs reverted to their normal flow speed within 12 h upon withdrawal of culture supernatant. Based on our observations, we suggest that the higher propensity of PRBCs and URBCs to slow down is due to inherent structural anisotropy and altered membrane rigidity. Thus the initial events leading to the slowing down of malaria-infected blood cells appear to be different from those occurring during leukocyte adhesion.